1. Field of the Invention
The present invention relates in general to a mass spectrometer and a mass spectrometry. Method, and more particularly to a mass spectrometer and a mass spectrometry method each of which employs an ion source for ionization entitled compounds contained in a solution.
2. Description of the Related Art
There is description of a sonic spray ionization method in an article of "Sonic Spray Ionization Method for Atmospheric Pressure Ionization Mass Spectrometry", Analytical Chemistry, Vol. 66, No. 24, Dec. 15, 1994, pp. 4557-4559. In the sonic spray ionization method, gas is caused to flow coaxially through a capillary from the outside of the capillary so as to spray the liquid through a tip of the capillary, thereby stably producing ions and charged droplets. In the case where the flow rate of gas at the tip of the capillary is substantially equal to the sonic velocity, an amount of positive and negative ions produced by the spray becomes maximum. In this case, neither an electric field nor discharge is applied to the liquid. The sprayed fine droplets thus produced are neutral in polarity as a whole and hence an amount of positive ions is substantially equal to an amount of negative ions.
In addition, there is description of an electrospray ionization method in an article entitled "Electrospray Ion Source. Another Variation on the Free-Jet Theme", Journal of Physical Chemistry, Vol. 88, No. 20, 1984, pp. 4451-4459, or U.S. Pat. No. 5,130,538. In the electrospray ionization method, a high voltage of 2.5 kV or more is applied to a metallic capillary into which the liquid is introduced and a counter electrode (corresponding in position to an inlet port for ions of a mass spectrometer). That is, the high voltage is applied to the liquid. As a result, the liquid is sprayed in the form of charged droplets through a tip of the capillary into a space in which an electric field is applied between the capillary and an counter electrode (the electrostatic spray phenomenon), thereby producing ions charged positive/negative from the charged droplets. In this connection, the polarity of the charged droplets and the ions matches the polarity of the applied voltage. In the electrospray ionization method, multiply-charged ions can be produced, and hence the electrospray ionization method is utilized for analysis of protein or the like in many cases. The flow rate of liquid is normally used in the range of 0.001 to 0.01 ml/min.
In addition, there is description of an ion spray ionization method in an article entitled "Ion Spray Interface for Combined Liquid Chromatography/Atmospheric Pressure Ionization Mass Spectrometry", Analytical Chemistry, Vol. 59, No. 22, Nov. 15, 1987, pp. 2642-2646, U.S. Pat. No. 4,861,988. In the ion spray ionization method, similarly to the electrospray ionization method, a high voltage of 2.5 kV or more is applied between the liquid at a tip of a spraying capillary and a counter electrode (corresponding in position to an inlet port for ions of a mass spectrometry unit). As a result, the liquid is sprayed in the form of ions and charged droplets through the tip of the capillary into a space in which an electric field is applied between the capillary and the counter electrode (the electrostatic spray phenomenon). In the ion spray ionization method, unlike the electrospray ionization method, gas is caused to flow into the outside of the spraying capillary in order to promote vaporization of the charged droplets. As a result, since the ions are produced utilizing the same electrostatic spray phenomenon, the ions thus produced are the same as those in the case of the electrospray ionization method at all. Thus, the polarity of the charged droplets and the ions matches that of the applied voltage. However, the flow rate of liquid is used in the range of 0.01 to 1 ml/min and it is larger than that in the electrospray ionization method. In addition, the flow rate of gas must not exceed 216 m/sec.
Further, there is description of an ionization method, in which when spraying liquid in the form of gas, a high voltage of 3.5 kV is applied to an electrode which is provided in the vicinity of a spraying portion, thereby producing charged droplets and ions, in an article entitled "Field induced ion evaporation from liquid surfaces at atmospheric pressure", Journal of Chemical Physics, Vol. 71, No. 11, Dec. 1, 1979, pp. 4451-4463, or U.S. Pat. No. 4,300,044. In this example, liquid and gas are respectively sprayed through an injection needle with 0.3 mm inner diameter. Unlike the sonic spray ionization method and the ion spray ionization method, however, the structure is adopted such that the direction of spraying the liquid is substantially perpendicular to the direction of the gas flow. The flow rate of the gas flow is not clear.
Now, when a mixture in solution is directly introduced to the mass spectrometer, it may be impossible in some cases to identify the mixture, since the resultant mass spectra are too complicated. For this reason, in the analysis of a mixture, a method is adopted in which the separation of the mixture in solution is firstly carried out using means such as a liquid chromatograph or a capillary electrophoresis system and the resultant extract is introduced into the mass spectrometer. That is, a liquid chromatograph/mass spectrometer and a capillary electrophoresis/mass spectrometer are present in each of which the separation and analysis of the mixture are realized online. In the liquid chromatograph, a solution is caused to flow through a column, which is packed with a material, by a pump at a fixed flow rate, thereby carrying out the separation of the mixture in solution. Therefore, an electric potential of the extract is the ground level. On the other hand, in the capillary electrophoresis system, a high voltage in the range of 20 to 30 kV or so is applied between the both ends of the capillary into which the solution is introduced, and then the mixture is separated on the basis of the electrophoresis. Normally, an electric potential at the outlet port side of the capillary is set to the ground level, and hence an electric potential of the extract is set to the ground level.
In the mass spectrometer, the analysis of the ion of interest is carried out on the basis of a value of m/z which is obtained by dividing the mass m of the ion by the charge number thereof z. The mass spectrometer in which the upper limit of the mass range of the mass spectrometry is very high is not suitable for practical use because of its large scale and its high cost. Therefore, in the general mass spectrometer, the upper limit of the mass range of the mass spectrometry is in the range of 1,000 to 2,000 or so in the value of m/z.
Now, in the above-mentioned prior art, the ions are mainly produced from the fine charged droplets. In the above-mentioned prior art relating to the electrospray ionization method and the ion spray ionization method, the charged droplets each having high density of electric charge are produced, and hence in the multiply-charged ions each having the charge state number z of 3 or more can be produced. Therefore, even in the case of the material, such as protein, having the giant mass m of several tens of thousands or so, the analysis thereof can be carried out since the value m/z is within the range of the mass spectrometry. However, the above-mentioned prior art relating to the sonic spray ionization method and the above-mentioned fourth prior art show a tendency in which the charged droplets each having low density of electric charge are produced and hence the ions each having the small charge state number are produced. That is, the production and the mass spectrometry of a singly-charged ion and a doubly-charged ion such as peptide can be made possible. However, in the analysis of the sample, such as protein, having the very large mass number m, since the multiply-charged ions each having the charge state number z of 3 or more can not be produced, the value of m/z departs from the mass range of the mass spectrometry and hence the mass analysis can not be carried out at all. This is a disadvantage.
In addition, in the above-mentioned prior art relating to the electrospray ionization method and the ion spray ionization method, the high voltage is applied to the liquid, and the ions and the charged droplets are produced on the basis of the electrostatic spray phenomenon. The large charged droplets each of which has low density of electric charge and the size of which is on the micron order as well as the fine charged droplets each having high density of electric charge are contained in the droplets which are produced on the basis of the above-mentioned phenomenon. The mass of the highly charged droplet is too large as compared with an amount of electric charge thereof, and hence it is difficult to control its movement by application of an electric field or a magnetic field. For this reason, when the mass spectrometry is carried out using a quadrupole mass spectrometer or a quadrupole ion trap mass spectrometer, the large charged droplets reach a detector without mass separation, and hence such droplets are detected in the form of random noises. In particular, the above-mentioned prior art relating to the ion spray ionization method shows a remarkable tendency that the highly charged droplets are readily produced since the flow rate of the liquid is high. The same problem is also applied to the above-mentioned fourth prior art. In the above-mentioned fourth prior art, the liquid is sprayed by assistance of the gas flow. However, the spraying portion adopts the structure such that the direction of spraying the liquid is substantially perpendicular to the direction of the gas flow. For this reason, a difference of the flow rate of the gas occurs between the upstream side of the gas flow and the downstream side of the gas flow at a tip of the injection needle through which the liquid is sprayed, and as a result, there arises a problem in dispersion in the droplet size that the size of the droplet becomes larger as the droplet is produced in the more downstream side. In addition, an electrode (an electrode 27 in FIG. 2 of U.S. Pat. No. 4,300,044) is constructed by one bar. For this reason, the density of electric charge of the droplet which is produced in a region, in the portion for spraying the liquid, in the vicinity of the electrode is different from the density of electric charge of the droplet which is produced in a region away therefrom. As a result, the large droplet having low density of electric charge is largely produced. In the above-mentioned fourth prior art, though the counter gas flow is generated at the inlet port for ions of the mass spectrometer in order to promote vaporization of the droplets, it is impossible to achieve the sufficient vaporization of the droplets. As described above, the ions are mainly produced from the fine charged droplet. In this connection, it is well known that the efficiency of producing ions is high as the size of the droplet is smaller. Then, the efficiency of producing ions from the large charged droplet is so low as to be able to be disregarded. As a result, there arises a problem that due to production of the large charged droplets, the sensitivity of detecting an ion is remarkably reduced by reduction of the intensity of a signal and increase of the noise level.
In addition, in the above-mentioned prior art relating to the electrospray ionization method and the ion spray ionization method, there is a problem, inherent in the electrostatic spray phenomenon, that it is necessary to adjust the position of the ion source whenever starting the spray in order to optimize the intensity of ions, and hence the operation for the system is complicated. This problem results from the fact that the electrostatic spray phenomenon shows the property that the shapes of the jet produced by spraying the solution vary remarkably due to contamination and wetting of the spraying capillary and the counter electrode (corresponding in position to the inlet port for ions of the mass spectrometry unit). Therefore, in the above-mentioned prior art relating to the electrospray ionization method and the ion spray ionization method, there arises a problem that the operation for the system requires a great deal of skill and hence the operating efficiency is extremely low.
In addition, in the above-mentioned prior art relating to the electrospray ionization method and the ion spray ionization method, in the case where the liquid chromatograph/mass spectrometer system or the capillary electrophoresis/mass spectrometer system is adopted in which the mixture separating means such as a liquid chromatograph or a capillary electrophoresis system is coupled to the upstream side thereof, since the high voltage is applied to the whole mixture separating means, there is a risk that during handling of the mixture separating means, an operator may get an electric shock in some cases. The electric potential of the whole mixture separating means may be set to the ground level when using the system in some cases. In such cases, the reproducibility of ion production and ion analysis is remarkably reduced since a sort of electrophoresis is realized in the capillary. For this reason, the liquid chromatograph/mass spectrometer system and the capillary electrophoresis/mass spectrometer system do not fulfill their functions in terms of operation as well as function. This is a problem.
In addition, each of the electrospray ionization method and the ion spray ionization method is a method wherein the voltage is directly applied to the sample solution, and by an electrostatic force occurring between the solution and the electrode of the mass spectrometer, the solution is sprayed so as to be ionized. Therefore, there arises a problem that when adding strong acid to the sample solution, since a current is caused to flow through the sample solution, no electrostatic spray phenomenon occurs and hence the ionization of the sample solution is difficult.